PMID- 35533251 OWN - NLM STAT- MEDLINE DCOM- 20220616 LR - 20220707 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 123 IP - 6 DP - 2022 Jun TI - Wnt/beta-catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork-derived mesenchymal stem cells. PG - 1120-1129 LID - 10.1002/jcb.30269 [doi] AB - Permanent degeneration and loss of dopaminergic (DA) neurons in substantia nigra is the main cause of Parkinson's disease. Considering the therapeutic application of stem cells in neurodegeneration, we sought to examine the neurogenic differentiation potential of the newly introduced neural crest originated mesenchymal stem cells (MSCs), namely, trabecular meshwork-derived mesenchymal stem cells (TM-MSCs) compared to two other sources of MSCs, adipose tissue-derived stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The three types of cells were therefore cultured in the presence and absence of a neural induction medium followed by the analysis of their differentiation potentials. Our results showed that TM-MSCs exhibited enhanced neural morphologies as well as higher expressions of MAP2 as the general neuron marker and Nurr-1 as an early DA marker compared to the adipose tissue-derived mesenchymal stem cells (AD-MSCs) and bone marrow-derived stem cells (BMSCs). Also, analysis of Nurr-1 immunostaining showed more intense Nurr-1 stained nuclei in the neurally induced TM-MSCs compared to those in the AD-MSCs, BMSCs, and noninduced control TM-MSCs. To examine if Wnt/beta-catenin pathway drives TM-MSCs towards a DA fate, we treated them with the Wnt agonist (CHIR, 3 muM) and the Wnt antagonist (IWP-2, 3 muM). Our results showed that the expressions of Nurr-1 and MAP2, as well as the Wnt/beta-catenin target genes, c-Myc and Cyclin D1, were significantly increased in the CHIR-treated TM-MSCs, but significantly reduced in those treated with IWP-2. Altogether, we declare first a higher neural potency of TM-MSCs compared to the more commonly used MSCs, BMSCs and ADSCs, and second that Wnt/beta-catenin activation directs the neurally induced TM-MSCs towards a DA fate. CI - (c) 2022 Wiley Periodicals LLC. FAU - Sahebdel, Faezeh AU - Sahebdel F AUID- ORCID: 0000-0003-4451-089X AD - Developmental Biology Laboratory, Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. FAU - Parvaneh Tafreshi, Azita AU - Parvaneh Tafreshi A AUID- ORCID: 0000-0003-1678-2863 AD - Developmental Biology Laboratory, Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. AD - Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. FAU - Arefian, Ehsan AU - Arefian E AUID- ORCID: 0000-0002-0758-4710 AD - Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran. FAU - Roussa, Eleni AU - Roussa E AUID- ORCID: 0000-0002-0495-1597 AD - Department of Molecular Embryology, Faculty of Medicine, Institute of Anatomy and Cell Biology, Albert Ludwigs University Freiburg, Freiburg, Germany. FAU - Nadri, Samad AU - Nadri S AD - Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. FAU - Zeynali, Bahman AU - Zeynali B AUID- ORCID: 0000-0001-6563-4969 AD - Developmental Biology Laboratory, Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. LA - eng GR - Iranian Vice Presidency for Science and Technology/ GR - University of Tehran/ GR - Iranian National Science Foundation/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220509 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (beta Catenin) SB - IM MH - Cell Differentiation MH - Cells, Cultured MH - *Mesenchymal Stem Cells/metabolism MH - Trabecular Meshwork/metabolism MH - *Wnt Signaling Pathway MH - beta Catenin/metabolism OTO - NOTNLM OT - Wnt/beta-catenin signaling pathway OT - dopaminergic differentiation OT - trabecular meshwork mesenchymal stem cells EDAT- 2022/05/10 06:00 MHDA- 2022/06/18 06:00 CRDT- 2022/05/09 14:35 PHST- 2022/04/20 00:00 [revised] PHST- 2021/07/02 00:00 [received] PHST- 2022/04/22 00:00 [accepted] PHST- 2022/05/10 06:00 [pubmed] PHST- 2022/06/18 06:00 [medline] PHST- 2022/05/09 14:35 [entrez] AID - 10.1002/jcb.30269 [doi] PST - ppublish SO - J Cell Biochem. 2022 Jun;123(6):1120-1129. doi: 10.1002/jcb.30269. Epub 2022 May 9.